Rate of Vaginal Cuff Dehiscence When Using Vicryl (Poliglactyn 910) Compared to PDS (Polydioxanone) for Vaginal Cuff Closure in Laparoscopic Hysterectomy.

Objective: To compare the vaginal cuff dehiscence (VCD) rates using Vicryl (Poliglactyn 910) and Polydioxanone (PDS) in patients who underwent laparoscopic hysterectomy. Materials and methods: A retrospective, monocentric study was conducted, including all patients undergoing laparoscopic hysterectomy at the Department of Obstetrics and Gynaecology, Azienda di Rilievo Nazionale e di Alta Specializzazione (ARNAS) Garibaldi Nesima, Catania, between January 2014 and December 2021. Patients underwent hysterectomy for benign gynecologic pathologies (endometriosis, leiomyomas, or benign pelvic pathologies) or malignant gynecologic pathologies (endometrium cancer, complex endometrial hyperplasia, ovarian cancer, cervix cancer, or uterine carcinosarcoma). The Z-score calculation was performed to find eventual statistically significant differences between the two populations regarding VCD rates. Results: Laparoscopic vaginal cuff closure was performed, with Vicryl sutures in 202 patients and PDS sutures in 184 women. Demographic and baseline characteristics were not significantly different in the two groups. VCD occurred in three patients in the Vicryl group and did not occur in the PDS group. The three cases of VCD were precipitated by intercourses that occurred within 90 days of surgery. However, there was not a significant statistical difference between the two groups regarding VCD (p = 0.09). Conclusions: Vicryl and PDS sutures seem to be similar for vaginal cuff closure in laparoscopic hysterectomy. The VCD rate was low, and the observed differences between the Vicryl and PDS groups did not reach statistical significance. Further research through prospective studies is essential.

Techniques and endocrine-reproductive outcomes of ovarian transposition prior to pelvic radiotherapy in both gynecologic and non-gynecologic cancers: A systematic review and meta-analysis.

BACKGROUND: Premature ovarian failure may be a consequence of radiotherapy administered for the treatment of various female oncologic diseases. Before radiotherapy, fertility may be preserved through ovarian transposition (OT), which consists of moving the ovaries away from the radiation field. OBJECTIVE: To ascertain all types of surgical techniques employed for OT, outline the endocrine and reproductive outcomes of each one, and discover if one works better than the others. SEARCH STRATEGY: The authors performed a systematic search of the English literature looking for all studies related to OT before radiotherapy published up to June 2023. Nine studies were included. SELECTION CRITERIA: The eligible studies were assessed based on the presence of a description of the surgical technique employed for OT before pelvic radiotherapy and a report of the endocrine and reproductive outcomes. DATA COLLECTION AND ANALYSIS: Odds ratios (OR) with 95% confidence intervals were used to compare endocrine and reproductive outcomes The χ2 test was employed for the statistical analysis and a P value less than 0.05 was considered significant. MAIN RESULTS: A total of 323 female patients aged between 7 and 51 years-198 (61.3%) with non-gynecologic cancer and 125 (38.7%) with gynecologic cancer-underwent OT, either bilateral (221, 68.4%) or unilateral (102, 31.6%), before radiotherapy. Essentially, two types of OT were employed: lateral and medial. A total of 71 (22%) patients underwent medial OT and 252 (78%) patients (127 with non-gynecologic tumors and 125 with gynecologic tumors) had a lateral OT. The latter was used in a similar percentage of cases for gynecologic (50.4%) and non-gynecologic (49.6%) tumors, whereas the medial approach was performed only for non-gynecologic cancers (Hodgkin's lymphoma). The difference between medial OT and lateral OT was not significant regarding the preservation of endocrine function (OR 0.65, P = 0.120). However, midline OT worked better in terms of reproductive outcomes. In fact, the percentage of patients with pregnancy (49.2%) and live births (45%) associated with medial OT was significantly higher than that associated with lateral OT, 6.5% and 13.4%, respectively, and the difference between such data was statistically significant (OR 7.04, P = 0.001 and OR 5.29, P = 0.003, respectively). CONCLUSIONS: Ovarian transposition is an important method to preserve fertility before radiotherapy, considering the worldwide ongoing use of this treatment for various cancers arising in young women. The surgical method depends on the type of disease, but OT-especially medial OT when feasible-is effective in terms of ovarian function preservation and reproductive outcomes.

Interleukin-6 as A Useful Predictor of Endometriosis-Associated Infertility: A Systematic Review.

Endometriosis is a chronic inflammatory disease defined by the presence of endometrial-like tissue outside the uterine cavity. Several authors have reported on the association between changes in inflammatory marker levels and the maintenance or progression of endometriosis and associated infertility. Interleukin-6 (IL-6) is the most studied cytokine in endometriosis and has important functions in reproductive physiology. The aim of this study is to review systematically available evidence about altered IL-6 concentrations in endometriosis-related infertility. This is a systematic review including all studies until December 2022 in which IL-6 in serum, peritoneal fluid, follicular fluid, or endometrial biopsy specimens was measured and that correlated their findings with endometriosis- associated infertility. Fifteen studies were included in the systematic review. There seems to be a correlation between elevated serum and peritoneal fluid IL-6 concentrations and the occurrence of endometriosis-associated infertility. IL-6 may be a potential diagnostic or biomarker tool for the prediction of endometriosis-related infertility. However, the numerous biases affecting the available studies, and challenges in endometriosis research reproducibility must be considered. Future investigations should pay attention to factors that may affect the results, such as the choice of suitable control groups, and carefully consider other pathological conditions affecting the patients, endometriosis stage, and type of lesion.

"Nutripiatto": A tool for nutritional education. A survey to assess dietary habits in preschool children.

Childhood obesity is a global public health concern linked to metabolic and psychological comorbidities. There is growing evidence that children's lifestyle habits are shifting towards obesity, with dire consequences for their future well-being and healthcare costs. In this interventional study, we enrolled 115 children aged between 4-5 years (53% females and 47% males) and carried out nutrition education interventions to improve their dietary habits. We introduced "Nutripiatto", a visual plate icon and easy guide, which was used by the children during the study. We investigated the children's dietary habits using a Food Frequency Questionnaire at the beginning and end of the study, after one month of using "Nutripiatto". The results showed that the children significantly increased the portion sizes and frequency of vegetable consumption (P<0.001) and reduced the consumption of several junk foods such as French fries and crisps (P<0.001), reaching the recommended dietary allowances and frequency of consumption. Daily consumption of water also significantly increased, reaching the suggested amount of six glasses per day. Based on these results, "Nutripiatto" can be considered an effective visual guide and helpful tool to achieve small changes and empower families to make healthier food choices. It can also be considered an effective educational tool for nutritionists and healthcare professionals to improve children's dietary behavior.

Implications of Possible HBV-Driven Regulation of Gene Expression in Stem Cell-like Subpopulation of Huh-7 Hepatocellular Carcinoma Cell Line.

Elevated levels of STIM1, an endoplasmic reticulum Ca2+ sensor/buffering protein, appear to be correlated with poor cancer prognosis in which microRNAs are also known to play critical roles. The purpose of this study is to investigate possible HBV origins of specific microRNAs we identified in a stem cell-like subpopulation of Huh-7 hepatocellular carcinoma (HCC) cell lines with enhanced STIM1 and/or Orai1 expression that mimicked poor cancer prognosis. Computational strategies including phylogenetic analyses were performed on miRNome data we obtained from an EpCAM- and CD133-expressing Huh-7 HCC stem cell-like subpopulation with enhanced STIM1 and/or Orai1 expression originally cultured in the present work. Results revealed two putative regions in the HBV genome based on the apparent clustering pattern of stem loop sequences of microRNAs, including miR3653. Reciprocal analysis of these regions identified critical human genes, of which their transcripts are among the predicted targets of miR3653, which was increased significantly by STIM1 or Orai1 enhancement. Briefly, this study provides phylogenetic evidence for a possible HBV-driven epigenetic remodeling that alters the expression pattern of Ca2+ homeostasis-associated genes in STIM1- or Orai1 overexpressing liver cancer stem-like cells for a possible mutual survival outcome. A novel region on HBV-X protein may affect liver carcinogenesis in a genotype-dependent manner. Therefore, detection of the viral genotype would have a clinical impact on prognosis of HBV-induced liver cancers.

Interpatient variability in the pharmacokinetics of remdesivir and its main metabolite GS-441524 in treated COVID-19 subjects.

BACKGROUND: Remdesivir is the first antiviral drug against SARS-CoV-2 approved for use in COVID-19 patients. OBJECTIVES: To study the pharmacokinetic inter-individual variability of remdesivir and its main metabolite GS-441524 in a real-world setting of COVID-19 inpatients and to identify possible associations with different demographic/biochemical variables. METHODS: Inpatients affected by SARS-CoV-2 infections, undergoing standard-dose remdesivir treatment, were prospectively enrolled. Blood samples were collected on day 4, immediately after (C0) and at 1 h (C1) and 24 h (C24) after infusion. Remdesivir and GS-441524 concentrations were measured using a validated UHPLC-MS/MS method and the AUC0-24 was calculated. At baseline, COVID-19 severity (ICU or no ICU), sex, age, BMI and renal and liver functions were assessed. Transaminases and estimated glomerular filtration rate (e-GFR) were also evaluated during treatment. Linear regression, logistic regression and multiple linear regression tests were used for statistical comparisons of pharmacokinetic parameters and variables. RESULTS: Eighty-five patients were included. The mean (CV%) values of remdesivir were: C0 2091 (99.1%) ng/mL, C1 139.7 (272.4%) ng/mL and AUC0-24 2791 (175.7%) ng·h/mL. The mean (CV%) values of GS-441524 were: C0 90.2 (49.5%) ng/mL, C1 104.9 (46.6%) ng/mL, C24 58.4 (66.9) ng/mL and AUC0-24 1976 (52.6%) ng·h/mL. The multiple regression analysis showed that age (P < 0.05) and e-GFR (P < 0.01) were independent predictors of GS-441524 plasma exposure. CONCLUSIONS: Our results showed a high interpatient variability of remdesivir and GS-441524 likely due to both age and renal function in COVID-19 inpatients. Further research is required to understand whether the pharmacokinetics of remdesivir and its metabolites may influence drug-related efficacy or toxic effect.

Role of BRCA Mutation and HE4 in Predicting Chemotherapy Response in Ovarian Cancer: A Retrospective Pilot Study.

Even though 80% of patients with High-Grade Serous Ovarian Cancer respond to standard first-line chemotherapy, a majority of them could relapse in the following five years due to a resistance to platinum. Human Epididymis protein 4 (HE4) is one of the most promising markers in predicting platinum therapy response. This pilot study aims to evaluate the potential role of HE4 value in predicting chemotherapy response in BRCA mutated patients and in BRCA wild-type (non-mutated) ones. We selected 69 patients, affected by High-Grade Serous Ovarian Cancer, and optimally debulked and submitted to standard chemotherapy protocols. HE4 was dosed during every chemotherapy course. Patients were classified as platinum-resistant and platinum-sensitive. According to BRCA mutation test, patients were further divided into BRCA wild-type (53 patients), and BRCA mutated (16 patients). 35 patients out of 69 (52%) were platinum-sensitive (recurrence > 12 months), while 33 patients (48%) were platinum-resistant (recurrence < 12 months). Thus, in the total population, HE4 performed as a marker of chemosensitivity with a sensibility of 79% and a specificity of 97%. In the BRCA WT group, 23 patients out of 53 (43%) were platinum-sensitive, while 30 patients out of 53 (57%) were platinum-resistant. In the BRCA WT group, HE4 performed as a predictive marker of chemosensitivity with a sensibility of 80% and a specificity of 100%. In the BRCA mutated group, 13 patients out of 16 (82%) were platinum-sensitive, while 3 patients (18%) were platinum-resistant. In the BRCA mutated group, HE4 performed as a predictive marker of chemosensitivity in all patients. The ability to detect platinum-resistant patients before tumor relapse probably could open new therapeutic scenarios.

What About Gastric Schwannoma? A Review Article.

PURPOSE: Gastric schwannomas (GSs) are rare mesenchymal neoplasms of the gastrointestinal tract. Diagnosis is often achieved postoperatively, based on pathology reports of retrieved specimens. The aim of the present study is to follow up all patients with gastric schwannoma (Gs) undergoing endoscopic, partial, or more extended surgery and to evaluate the appearance of local or distant recurrence. METHODS: A PubMed, Cochrane, and Embase systematic review of the literature has been performed. Original papers, review articles, and case reports published between 1988 and 2019 were considered eligible. All the studies who met the inclusion criteria were analyzed. Statistical analysis of data has been performed using GraphPad Prism 7 software. RESULTS: Three hundred twenty-eight articles were found, and a total of 102 were included and analyzed in depth. Fifty-three papers reported the follow-up information, ranging from 1 to 417 months across different studies. Among them, 31 patients underwent endoscopic removal of the gastric lesions; 140 patients underwent local surgery, including wedge resection or partial gastrectomy; and 148 patients underwent subtotal or total gastrectomy. The median follow-up was of 27-38-33 months, respectively. No recurrence or distant metastasis was detected in the endoscopy group. Among local surgery group, liver metastasis was reported in one case; in extended surgery group, one patient died for multiple liver metastases. CONCLUSIONS: Local or more extended surgery involved a larger cohort of patients and reported satisfactory long-term results compared with endoscopy group. Surgery in absence of a definite preoperative diagnosis is considered the gold standard treatment for resectable Gs.

Best diagnostic accuracy of sepsis combining SIRS criteria or qSOFA score with Procalcitonin and Mid-Regional pro-Adrenomedullin outside ICU.

Early diagnosis and treatment significantly reduce sepsis mortality. Currently, no gold standard has been yet established to diagnose sepsis outside the ICU. The aim of the study was to evaluate the diagnostic accuracy of sepsis defined by SIRS Criteria of 1991, Second Consensus Conference Criteria of 2001, modified Second Consensus Conference Criteria of 2001 (obtaining SIRS Criteria and SOFA score), Third Consensus Conference of 2016, in addition to the dosage of Procalcitonin (PCT) and MR-pro-Adrenomedullin (MR-proADM). In this prospective study, 209 consecutive patients with clinical diagnosis of sepsis were enrolled (May 2014-June 2018) outside intensive care unit (ICU) setting. A diagnostic protocol could include SIRS criteria or qSOFA score evaluation, rapid testing of PCT and MR-proADM, and SOFA score calculation for organ failure definition. Using this approach outside the ICU, a rapid diagnostic and prognostic evaluation could be achieved, also in the case of negative SIRS, qSOFA or SOFA scores with high post-test probability to reduce mortality and improve outcomes.

Sars-CoV-2 Envelope and Membrane Proteins: Structural Differences Linked to Virus Characteristics?

The Coronavirus Disease 2019 (COVID-19) is a new viral infection caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2). Genomic analyses have revealed that SARS-CoV-2 is related to Pangolin and Bat coronaviruses. In this report, a structural comparison between the Sars-CoV-2 Envelope and Membrane proteins from different human isolates with homologous proteins from closely related viruses is described. The analyses here reported show the high structural similarity of Envelope and Membrane proteins to the counterparts from Pangolin and Bat coronavirus isolates. However, the comparisons have also highlighted structural differences specific of Sars-CoV-2 proteins which may be correlated to the cross-species transmission and/or to the properties of the virus. Structural modelling has been applied to map the variant sites onto the predicted three-dimensional structure of the Envelope and Membrane proteins.

COVID-2019: The role of the nsp2 and nsp3 in its pathogenesis.

Last December 2019, a new virus, named novel Coronavirus (COVID-2019) causing many cases of severe pneumonia was reported in Wuhan, China. The virus knowledge is limited and especially about COVID-2019 pathogenesis. The Open Reading Frame 1ab (ORF1ab) of COVID-2019 has been analyzed to evidence the presence of mutation caused by selective pressure on the virus. For selective pressure analysis fast-unconstrained Bayesian approximation (FUBAR) was used. Homology modelling has been performed by SwissModel and HHPred servers. The presence of transmembrane helical segments in Coronavirus ORF1ab non structural protein 2 (nsp2) and nsp3 was tested by TMHMM, MEMSAT, and MEMPACK tools. Three-dimensional structures have been analyzed and displayed using PyMOL. FUBAR analysis revealed the presence of potential sites under positive selective pressure (P < .05). Position 723 in the COVID-2019 has a serine instead a glycine residue, while at aminoacidic position 1010 a proline instead an isoleucine. Significant (P < .05) pervasive negative selection in 2416 sites (55%) was found. The positive selective pressure could account for some clinical features of this virus compared with severe acute respiratory syndrome (SARS) and Bat SARS-like CoV. The stabilizing mutation falling in the endosome-associated-protein-like domain of the nsp2 protein could account for COVID-2019 high ability of contagious, while the destabilizing mutation in nsp3 proteins could suggest a potential mechanism differentiating COVID-2019 from SARS. These data could be helpful for further investigation aimed to identify potential therapeutic targets or vaccine strategy, especially in the actual moment when the epidemic is ongoing and the scientific community is trying to enrich knowledge about this new viral pathogen.

The transmission dynamic of Madariaga Virus by bayesian phylogenetic analysis: Molecular surveillance of an emergent pathogen.

Madariaga Virus (MADV) is an emergent Alphavirus of the eastern equine encephalitis virus (EEEV) strain complex causing epizootic epidemics. In this study the genetic diversity and the transmission dynamics of Madariaga virus has been investigated by Bayesian phylogenetics and phylodynamic analysis. A database of 32 sequences of MADV group structural polyprotein were downloaded from GenBank, aligned manually edited by Bioedit Software. ModelTest v. 3.7 was used to select the simplest evolutionary model that adequately fitted the sequence data. Neighbor-joining tree was generated using MEGA7. The phylogenetic signal of the dataset was tested by the likelihood mapping analysis. The Bayesian phylogenetic tree was built using BEAST. Selective pressure analysis revealed one positive selection site. The phylogenetic trees showed two main clusters. In particular, Lineage II showed an epizootic infection in monkeys and Lineage III, including 2 main clusters (IIIa and IIIB), revealing an epizootic infection in humans in Haiti and an epizootic infection in humans in Venezuela during the 2016, respectively. The Bayesian maximum clade credibility tree and the time of the most common recent ancestor estimates, showed that the root of the tree dated back to the year 346 with the probable origin in Brazil. Gene flow analysis revealed viral exchanges between different neighbor countries of South America. In conclusion, Bayesian phylogenetic and phylodynamic represent useful tools to follow the transmission dynamic of emergent pathogens to prevent new epidemics spreading worldwide.

Efficacy of radiofrequency ablation in autonomous functioning thyroid nodules. A systematic review and meta-analysis.

Whether thermal ablation is effective to treat toxic thyroid nodules (TTN) is still unknown. Aim of this review was to achieve more robust evidence on the efficacy of radiofrequency ablation (RFA) in treating TTN in terms of TSH normalization, thyroid scintiscan, and volume reduction rate (VRR). A comprehensive literature search of PubMed/Medline and Scopus was performed in November 2018 to retrieve published studies. Original papers reporting TTN treated by RFA and later followed-up were eligible. Excluded were: articles not within this field, articles with unclear data, overlapping series, case/series reports. Discordances were solved in a final collegial meeting. Information was collected concerning population features, treatment procedure, follow-up, cases with TSH normalization, cases with scintiscan normalization, VRR of nodules. Pooled prevalence of patients with TSH or scintiscan normalization, and pooled VRR over time were calculated. For statistical analysis, the random-effects model was used. Eight articles published between 2008 and 2018 were included. The overall number of AFTN treated by RFA was 205. Five studies used a single session of treatment. The time of follow-up ranged from six to 24 months. The pooled rate of patients with TSH normalization was 57%. The pooled rate of patients with scintigraphically proven optimal response was 60%. The pooled VRR at 1 year was 79%. Baseline nodules volume was associated with the rate of TSH normalization. In conclusion, a moderate efficacy of RFA in treating TTN was found, and this can represent a solid starting point in this field.

Hybrid approach to thoracic aortic aneurysm: The Lupiae technique.

Aortic diseases, especially when the entire aorta is involved, are often challenging to treat since they frequently require invasive interventions. Minimally invasive hybrid treatment of such pathologies is proving to be a valid option for complex cases (for example, dilation involving the entire aorta) and is improving postoperative outcomes. It consists of a minimally invasive opening stage, where ascending aorta and aortic arch replacement and epiaortic vessel rerouting is performed using a multibranched graft equipped with a radiopaque marker. This is followed by an endovascular stage, where the remaining diseased aorta is covered with an endoprosthesis. This procedure has been described as Lupiae technique and the results seem encouraging.  In this tutorial, we give a practical overview of this technique, describing the treatment of a particular condition called mega-aorta syndrome type 1, which is the dilation of the aorta up to celiac trunk.

Risk factors for silent myocardial ischemia in patients with well-controlled essential hypertension.

Silent myocardial ischemia (SMI) is frequently observed in patients with essential hypertension (EH). The major risk factor for SMI is uncontrolled blood pressure (BP), but SMI is also observed in patients with well-controlled BP. To evaluate the prevalence of SMI and the factors associated with SMI in EH patients with well-controlled BP. The medical records of 859 EH patients who underwent simultaneous 24-h ambulatory blood pressure monitoring (ABPM) and 24-h ambulatory electrocardiogram recording (AECG) were retrospectively evaluated. Each SMI episode was characterized by: (a) ST segment depression ≥0.5 mm; (b) duration of ST segment depression >60 s; and (c) reversibility of the ST segment depression. Overall 126 EH patients (14.7 %) had at least one episode of SMI. The SMI events were more frequent among patients with poorly controlled compared to those with well-controlled BP [86/479 (17.95 %) vs. 40/380 (10.52 %), p < 0.01]. Among EH patients with well-controlled BP, current and past smoking as well as the presence of an additional metabolic syndrome (MetS) constitutive element (obesity, impaired fasting glucose level or dyslipidemia) were significantly associated with the occurrence of SMI. In all EH patients with well-controlled BP and AECG evidence of SMI, there were one or more coronary artery stenotic lesions greater than 50 % found at coronary angiography. In EH patients who are current smokers, or have one or more additional components of a MetS there is markedly reduced benefit associated with good BP control with regard to the occurrence of myocardial ischemia: in this patient category, an AECG may help detect this condition.

Thyrocervical trunk pseudoaneurysm following central venous catheterization.

A 71-year-old female developed a painless neck mass three months following an aortic valve replacement, mitral commissurotomy, and coronary artery bypass. A cervical trunk angio revealed a pseudoaneurysm supplied from a branch of the thyrocervical trunk, which was successfully excised.